Recombination rate and selection strength in HIV intra-patient evolution

The evolutionary dynamics of HIV during the chronic phase of infection is driven by the host immune response and by selective pressures exerted through drug treatment. To understand and model the evolution of HIV quantitatively, the parameters governing genetic diversification and the strength of selection need to be known. While mutation rates can be measured in single replication cycles, the relevant effective recombination rate depends on the probability of coinfection of a cell with more than one virus and can only be inferred from population data. However, most population genetic estimators for recombination rates assume absence of selection and are hence of limited applicability to HIV, since positive and purifying selection are important in HIV evolution. Here, we estimate the rate of recombination and the distribution of selection coefficients from time-resolved sequence data tracking the evolution of HIV within single patients. By examining temporal changes in the genetic composition of the population, we estimate the effective recombination to be r=1.4e-5 recombinations per site and generation. Furthermore, we provide evidence that selection coefficients of at least 15% of the observed non-synonymous polymorphisms exceed 0.8% per generation. These results provide a basis for a more detailed understanding of the evolution of HIV. A particularly interesting case is evolution in response to drug treatment, where recombination can facilitate the rapid acquisition of multiple resistance mutations. With the methods developed here, more precise and more detailed studies will be possible, as soon as data with higher time resolution and greater sample sizes is available.Comment: to appear in PLoS Computational Biolog

Limits to the Rate of Adaptive Substitution in Sexual Populations

In large populations, many beneficial mutations may be simultaneously available and may compete with one another, slowing adaptation. By finding the probability of fixation of a favorable allele in a simple model of a haploid sexual population, we find limits to the rate of adaptive substitution, , that depend on simple parameter combinations. When variance in fitness is low and linkage is loose, the baseline rate of substitution is , where is the population size, is the rate of beneficial mutations per genome, and is their mean selective advantage. Heritable variance in log fitness due to unlinked loci reduces by under polygamy and under monogamy. With a linear genetic map of length Morgans, interference is yet stronger. We use a scaling argument to show that the density of adaptive substitutions depends on , , , and only through the baseline density: . Under the approximation that the interference due to different sweeps adds up, we show that , implying that interference prevents the rate of adaptive substitution from exceeding one per centimorgan per 200 generations. Simulations and numerical calculations confirm the scaling argument and confirm the additive approximation for ; for higher , the rate of adaptation grows above , but only very slowly. We also consider the effect of sweeps on neutral diversity and show that, while even occasional sweeps can greatly reduce neutral diversity, this effect saturates as sweeps become more common—diversity can be maintained even in populations experiencing very strong interference. Our results indicate that for some organisms the rate of adaptive substitution may be primarily recombination-limited, depending only weakly on the mutation supply and the strength of selection

Galaxy Collisions - Dawn of a New Era

The study of colliding galaxies has progressed rapidly in the last few years, driven by observations with powerful new ground and space-based instruments. These instruments have used for detailed studies of specific nearby systems, statistical studies of large samples of relatively nearby systems, and increasingly large samples of high redshift systems. Following a brief summary of the historical context, this review attempts to integrate these studies to address the following key issues. What role do collisions play in galaxy evolution, and how can recently discovered processes like downsizing resolve some apparently contradictory results of high redshift studies? What is the role of environment in galaxy collisions? How is star formation and nuclear activity orchestrated by the large scale dynamics, before and during merger? Are novel modes of star formation involved? What are we to make of the association of ultraluminous X-ray sources with colliding galaxies? To what do degree do mergers and feedback trigger long-term secular effects? How far can we push the archaeology of individual systems to determine the nature of precursor systems and the precise effect of the interaction? Tentative answers to many of these questions have been suggested, and the prospects for answering most of them in the next few decades are good.Comment: 44 pages, 9 figures, review article in press for Astrophysics Update Vol.

Limits on Gravitational-Wave Emission from Selected Pulsars Using LIGO Data

We place direct upper limits on the amplitude of gravitational waves from 28 isolated radio pulsars by a coherent multidetector analysis of the data collected during the second science run of the LIGO interferometric detectors. These are the first direct upper limits for 26 of the 28 pulsars. We use coordinated radio observations for the first time to build radio-guided phase templates for the expected gravitational-wave signals. The unprecedented sensitivity of the detectors allows us to set strain upper limits as low as a few times 10^(-24). These strain limits translate into limits on the equatorial ellipticities of the pulsars, which are smaller than 10^(-5) for the four closest pulsars

The Properties of Adaptive Walks in Evolving Populations of Fungus

A novel method to infer the number and fitness effect of beneficial mutations reveals that the bulk of adaptive evolution is attributable to a few mutations with variable effects on fitness

Optimal Strategy for Competence Differentiation in Bacteria

A phylogenetically diverse subset of bacterial species are naturally competent for transformation by DNA. Transformation entails recombination of genes between different lineages, representing a form of bacterial sex that increases standing genetic variation. We first assess whether homologous recombination by transformation is favored by evolution. Using stochastic population genetic computer simulations in which beneficial and deleterious mutations occur at many loci throughout the whole genome, we find that transformation can increase both the rate of adaptive evolution and the equilibrium level of fitness. Secondly, motivated by experimental observations of Bacillus subtilis, we assume that competence additionally entails a weak persister phenotype, i.e., the rates of birth and death are reduced for these cells. Consequently, persisters evolve more slowly than non-persisters. We show via simulation that strains which stochastically switch into and out of the competent phenotype are evolutionarily favored over strains that express only a single phenotype. Our model's simplicity enables us to derive and numerically solve a system of finite- deterministic equations that describe the evolutionary dynamics. The observed tradeoff between the benefit of recombination and the cost of persistence may explain the previously mysterious observation that only a fractional subpopulation of B. subtilis cells express competence. More generally, this work demonstrates that population genetic forces can give rise to phenotypic diversity even in an unchanging and homogeneous environment

History of Galaxy Interactions and their Impact on Star Formation over the Last 7 Gyr from GEMS

We perform a comprehensive estimate of the frequency of galaxy mergers and their impact on star formation over z~0.24--0.80 (lookback time T_b~3--7 Gyr) using 3698 (M*>=1e9 Msun) galaxies with GEMS HST, COMBO-17, and Spitzer data. Our results are: (1) Among 790 high mass (M*>=2.5e10 Msun) galaxies, the visually-based merger fraction over z~0.24--0.80, ranges from 9%+-5% to 8%+-2%. Lower limits on the major and minor merger fractions over this interval range from 1.1% to 3.5%, and 3.6% to 7.5%, respectively. This is the first approximate empirical estimate of the frequency of minor mergers at z<1. For a visibility timescale of ~0.5 Gyr, it follows that over T_b~3--7 Gyr, ~68% of high mass systems have undergone a merger of mass ratio >1/10, with ~16%, 45%, and 7% of these corresponding respectively to major, minor, and ambiguous `major or minor' mergers. The mean merger rate is a few x 1e-4 Gyr-1 Mpc-3. (2) We compare the empirical merger fraction and rate for high mass galaxies to a suite of Lambda CDM-based models: halo occupation distribution models, semi-analytic models, and hydrodynamic SPH simulations. We find qualitative agreement between observations and models such that the (major+minor) merger fraction or rate from different models bracket the observations, and show a factor of five dispersion. Near-future improvements can now start to rule out certain merger scenarios. (3) Among ~3698 M*>=1e9 Msun galaxies, we find that the mean SFR of visibly merging systems is only modestly enhanced compared to non-interacting galaxies over z~0.24--0.80. Visibly merging systems only account for less than 30% of the cosmic SFR density over T_b~3--7 Gyr. This suggests that the behavior of the cosmic SFR density over the last 7 Gyr is predominantly shaped by non-interacting galaxies.Comment: Accepted for Publication in the Astrophysical Journal. 17 pages of text, 21 figures, 3 tables. Uses emulateapj5.st

Searching for gravitational waves from known pulsars

We present upper limits on the amplitude of gravitational waves from 28 isolated pulsars using data from the second science run of LIGO. The results are also expressed as a constraint on the pulsars' equatorial ellipticities. We discuss a new way of presenting such ellipticity upper limits that takes account of the uncertainties of the pulsar moment of inertia. We also extend our previous method to search for known pulsars in binary systems, of which there are about 80 in the sensitive frequency range of LIGO and GEO 600.Comment: Accepted by CQG for the proceeding of GWDAW9, 7 pages, 2 figure

First upper limits from LIGO on gravitational wave bursts

We report on a search for gravitational wave bursts using data from the first science run of the LIGO detectors. Our search focuses on bursts with durations ranging from 4 ms to 100 ms, and with significant power in the LIGO sensitivity band of 150 to 3000 Hz. We bound the rate for such detected bursts at less than 1.6 events per day at 90% confidence level. This result is interpreted in terms of the detection efficiency for ad hoc waveforms (Gaussians and sine-Gaussians) as a function of their root-sum-square strain h_{rss}; typical sensitivities lie in the range h_{rss} ~ 10^{-19} - 10^{-17} strain/rtHz, depending on waveform. We discuss improvements in the search method that will be applied to future science data from LIGO and other gravitational wave detectors.Comment: 21 pages, 15 figures, accepted by Phys Rev D. Fixed a few small typos and updated a few reference